Plasma-derived proteins in airway defence, disease and repair of epithelial injury

Abstract

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.

Effects of experimental changes in nasal airway pressure on mucosal output of plasma

“…The baseline appearance of a 2 -macroglobulin was low and consistent with previously reported baseline levels (Persson et al, 1998;Greiff et al, 2002). Furthermore, histamine produced an expected, marked mucosal output of a 2 -macroglobulin (P<0AE001).…”

“…Although this process involves movement of bulk plasma, including the largest plasma proteins such as a 2 -macroglobulin (this study), the luminal entry may not damage the epithelial lining (Erjefält et al, 1995), nor does it increase mucosal absorption, i.e. the perviousness of the epithelium to luminal solutes (Greiff et al, 1991a,b;Persson et al, 1998). We have previously suggested that this unidirectional increase in the outward permeability of the epithelial lining reflects a hydrostatic pressure-operated valve-like mechanism whereby a slight increase in the subepithelial hydrostatic pressure, created by the plasma exudate itself and its attracted fluids, allows epithelial cells to transiently separate.…”

“…We have demonstrated that the plasma exudate rapidly enters the airway lumen, and we have suggested that plasma also moves across the epithelial lining aided by a pressure-operated mechanism, allowing epithelial cells to separate transiently and plasma to move into the airway lumen via a paracellular routes (Erjefält & Persson, 1989;Persson et al, 1998). This hypothesis is supported by observations in vitro demonstrating that application of a slight hydrostatic pressure (5 cmH 2 O) on the serosal aspect of guinea-pig tracheal tube preparations readily produces luminal entry of macromolecules Gustafsson & Persson, 1991).…”

“…van der Graaf et al, 1991). The most important implication may be that adhesive, leucocyte-activating, growth-factor active, complement-active, and otherwise biologically active plasma proteins will promptly operate in and on an insulted but still intact airway mucosa (Persson et al, 1998).…”

“…Microvascular extravasation, lamina propria flooding and luminal entry of bulk plasma are key features of airway inflammation (Persson et al, 1998). Accordingly, topical airway applications of various inflammatory mediators, including histamine, produce increased levels of different-sized plasma proteins in airway mucosal surface liquids (Greiff et al, 2002).…”